project . 2009 - 2011 . Closed

Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt pathways.

Wellcome Trust
  • Funder: Wellcome TrustProject code: 088145
  • Funded under: Neuroscience and Mental Health Funder Contribution: 113,474 GBP
  • Status: Closed
  • Start Date
    01 Oct 2009
    End Date
    31 Jul 2011
Description
Mutations in PARK8, encoding LRRK2, are the most frequent known cause of Parkinson's disease. LRRK2 is a cytosolic protein kinase that is regulated by a Roc-COR tandem domain with intrinsic GTPase activity. Modification of LRRK2 GTPase and kinase activity by familial PD mutations in the Roc, COR and kinase domains leads to neuronal death, but the pathways involved remain elusive. For example, it is unclear how LRRK2 GTPase activity is regulated in vivo. I present compelling evidence that LRRK2 i nteracts with dishevelled (DVL) family phosphoproteins (DVL1-3), key regulators of Wnt (Wingless/Int) signalling pathways, and that pathogenic mutations in the LRRK2 Roc...
Description
Mutations in PARK8, encoding LRRK2, are the most frequent known cause of Parkinson's disease. LRRK2 is a cytosolic protein kinase that is regulated by a Roc-COR tandem domain with intrinsic GTPase activity. Modification of LRRK2 GTPase and kinase activity by familial PD mutations in the Roc, COR and kinase domains leads to neuronal death, but the pathways involved remain elusive. For example, it is unclear how LRRK2 GTPase activity is regulated in vivo. I present compelling evidence that LRRK2 i nteracts with dishevelled (DVL) family phosphoproteins (DVL1-3), key regulators of Wnt (Wingless/Int) signalling pathways, and that pathogenic mutations in the LRRK2 Roc...
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